Development of Novel Nano-Elastic Carriers for Trametinib Delivery in Melanoma Treatment

Abstract

Trametinib (TM), an inhibitor of mitogen-activated extracellular signal-regulatory kinase (ERK), is a clinically licensed targeted therapy by the Food and Drug Administration (FDA) for treating refractory malignancies with BRAF-V600E gene mutations, such as melanoma and advanced lung adenocarcinoma. Nonetheless, the commercial Tr is constrained in clinical applications due to its low solubility, absence of bio-targeting, and a significant concern is its propensity to generate multidrug resistance in tumour cells. The produced formulations demonstrated that the optimal results were achieved with a high concentration of the mucoadhesive polymer chitosan (0.5 and 1% w/v). The chitosan-coated bilosomes (TM-CBLs) were subsequently assessed for surface morphology, antioxidant activity, and antibacterial activity. The synthesised TM-BLs exhibited a nanometric size ranging from 185.34±5.28 nm (BS3) to 295.31±6.31 nm (BS5), a polydispersity index of less than 0.5, a negative zeta potential of -10.74±1.06 mV and -21.54±1.42 mV, and an improved encapsulation efficiency of 56.49±0.16% to 80.27±0.64%. According to these findings, the chosen formulation (BS2) was subsequently coated with chitosan, resulting in a significant increase in vesicle size (268.49±2.31nm), a positive zeta potential (17.36±0.52 mV), enhanced encapsulation efficiency (87.35±0.26%), and increased drug release (69.37 ± 1.34%). The TM-CBLs formulation exhibited markedly improved permeability and mucoadhesion (p < 0.05) relative to the BS2 formulation, attributable to the inclusion of chitosan as a mucoadhesive polymer. The evaluation of antibacterial and antioxidant activity demonstrated superior benefits regarding the zone of inhibition. The study concludes that TM-BLs may serve as a superior alternative to traditional delivery techniques.